Strategies to inhibit viral protein nuclear import: HIV-1 as a target

Nuclear import is a critical step in the life cycle of HIV-1. During the early (preintegration) stages of infection, HIV-1 has to transport its preintegration complex into the nucleus for integration into the host cell chromatin, while at the later (postintegration) stages viral regulatory proteins Tat and Rev need to get into the nucleus to stimulate transcription and regulate splicing and nuclear export of subgenomic and genomic RNAs. Given such important role of nuclear import in HIV-1 life cycle, this step presents an attractive target for antiviral therapeutic intervention. In this review, we describe the current state of our understanding of the interactions regulating nuclear import of the HIV-1 preintegration complex and describe current approaches to inhibit it. This article is part of a Special Issue entitled: Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import.

Research highlights
► Nuclear import is critical for HIV replication in both dividing and non-dividing cells.
► Nuclear import of the viral pre-integration complex is tightly linked to viral uncoating.
► HIV relies on cellular nuclear import machinery for transporting its pre-integration complex into the nucleus.
► The use of cellular nuclear import pathways by HIV may change depending on cell type or cell activation state.
► Different PIC proteins may regulate nuclear import under different circumstances.